An In-Silico Investigation of Key Lysine Residues and Their Selection for Clearing off A β and Holo-AβPP Through Ubiquitination

AbstractMalicious progression of neurodegeneration is a consequence of toxic aggregates of proteins or peptides such as amyloid beta (A β) reported in Alzheimer’s disease (AD). These aggregates hinder the electrochemical transmission at neuronal junctions and thus deteriorate neuronal-health by triggering dementia. Electrostatic and hydrophobic interactions among amino-acid residues are the governing principle behind the self-ass embly of aforesaid noxious oligomers or agglomerate. Interestingly, lysine residues are crucial for these interactions and for facilitating the clearance of toxic metabolites through the ubiquitination process. The mechanisms behind lysine selectivity and modifications of target proteins are very in triguing process and an avenue to explore the clearance of unwanted proteins from neurons. Therefore, it is fascinating for the researchers to investigate the role of key lysine, their selectivity and interactions with other amino acids to clear-off toxic products in exempting the progression of Neu rodegenerative disorders (NDDs). Herein, (1) we identified the aggregation prone sequence in Aβ40 and Aβ42 as ‘HHQKLVFFAE’ and ‘SGYEVHHQKLVFFAEDVG/KGAIIGLMVGGV’ respectively with critical lysine (K) at 16 and 28 for stabilizing the aggregates; (2) elucidated the interaction pattern of AβP P with other Alzheimer’s related proteins BACE1, APOE, SNCA, APBB1, CASP8, NAE1, ADAM10, and PSEN1 to describe the pat...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research

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Publication date: Available online 26 February 2020Source: European Journal of Integrative MedicineAuthor(s): Jiao Lan, Ji-fei Miao, Shu-qi Ge, Tie-qu Chai, Chun-zhi Tang, Li-ming Lu
Source: European Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
AbstractThe use of psychotropic drugs (antipsychotics, benzodiazepines and benzodiazepine-related drugs, and antidepressants) is common, with a prevalence estimates range of 19 –29% among community dwelling older adults. These drugs are often prescribed for off-label use, including neuropsychiatric symptoms. The older adult population also has high rates of pneumonia and some of these cases may be associated with adverse drug events. In this narrative review, we summariz e the findings from current observational studies on the association between psychotropic drug use and pneumonia in older adults. In addition to stu...
Source: Drugs and Aging - Category: Geriatrics Source Type: research
ConclusionCitation searching using Scopus alone would have found all additional relevant studies for the review. Both Scopus and Web of Science failed to return all citing references from the source records, even where they were present on the database, indicating poor links between citations.This article is protected by copyright. All rights reserved.
Source: Research Synthesis Methods - Category: Chemistry Authors: Tags: RESEARCH ARTICLE Source Type: research
Conditions:   Dementia;   Alzheimer Disease;   Dementia, Vascular;   Lewy Body Disease;   Frontotemporal Lobar Degeneration;   Memory Disorders Intervention:   Behavioral: Navigated Care Sponsors:   University of California, San Francisco;   University of Nebraska;   National Institute on Aging (NIA);   Centers for Medicare and Medicaid Services Active, not recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions: PLWH with mood disorders were at increased risk of incident NCDs and multimorbidity, particularly metabolic syndrome. Focused prevention and treatment of NCDs may reduce the burden of multimorbidity in this high-risk group.
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - Category: Infectious Diseases Tags: Clinical Science Source Type: research
Early-onset dementia and Alzheimer ’s disease jumped 200% among commercially insured Americans between the ages of 30 and 64 over a recent five-year period, a new analysis of Blue Cross and Blue Shield health insurer claims shows.
Source: Forbes.com Healthcare News - Category: Pharmaceuticals Authors: Source Type: news
Objectives: Hearing impairment (HI) in midlife may increase the risk of dementia. However, epidemiological research on the association between HI and mild cognitive impairment (MCI) is very limited. Design: The present cross-sectional study investigated the relationship between HI and MCI using baseline data from the Aidai Cohort Study. Study subjects were 995 Japanese adults aged 36 to 84 years. We used the audiometric definition of HI adopted by the World Health Organization, which identifies the speech-frequency pure-tone average hearing thresholds at 0.5, 1, 2, and 4 kHz tones. HI was defined as present when pure-...
Source: Ear and Hearing - Category: Audiology Tags: Research Article Source Type: research
CONCLUSION: Only a small proportion of residents in LTCFs received hospice care. Further investigation of standardized assessment of terminal status is needed as accuracy of end-stage diagnosis continues to be challenging and criteria for hospice eligibility are narrow. Special attention should be paid to improve access to hospice care among residents with dementia or other progressive chronic diseases with severe and complex clinical needs. PMID: 32093589 [PubMed - as supplied by publisher]
Source: Journal of Palliative Care - Category: Palliative Care Tags: J Palliat Care Source Type: research
Atypical chest pain is of diverse origin. Typically, we initially consider cardiac etiology. When pain appears non-cardiac, there is a tendency to underestimate the illness, especially if the patient has neuropsychiatric illness. Our resident with dementia and anxiety disorder had chest pain; the diagnosis was unexpected.
Source: Journal of the American Medical Directors Association - Category: Health Management Authors: Source Type: research
Psychotropic medications are often prescribed to manage behavioral and psychological symptoms of dementia (BPSD) in nursing home (NH) residents, although these medications may lack efficacy for BPSD and can have adverse effects. NHs can receive a deficiency of care citation for inappropriate psychotropic medication use (F-758 tag). To promote more effective dementia care, some states specify dementia-specific training requirements for NH nursing staff. The occurrence of F-758 citations related to care of residents with dementia was examined in relation to the presence of state-level dementia-specific in-service training re...
Source: Journal of the American Medical Directors Association - Category: Health Management Authors: Source Type: research
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